Use of Swedish smokeless tobacco (snus) and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA).

AIMS: It has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). METHOD: Analyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population-based controls (n = 699) from a Swedish case-control study. Additional analyses were performed on cross-sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included. RESULTS: No association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box-years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever-users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83). CONCLUSION: The risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke.

Autoimmune diabetes in adults and risk of myocardial infarction: the HUNT study in Norway.

BACKGROUND: The long-term consequences of autoimmune diabetes in adults (AIDA) are largely unexplored. OBJECTIVE: To investigate the risk of myocardial infarction (MI) in AIDA compared to type 2 diabetes, taking into consideration the effects of socio-economic and lifestyle factors, the metabolic syndrome and glycaemic control. METHODS: A total of 62 995 participants including 207 individuals with AIDA (onset ≥35 years and anti-GAD positive) and 2322 individuals with type 2 diabetes (onset ≥35 years and anti-GAD negative), from the population-based Norwegian HUNT study, were followed for a first MI during the period 1995-2008. We identified 2614 MIs by hospital records or the National Cause of Death Registry. Cox proportional hazard models were used to estimate the risk of MI by diabetes subgroups after adjustment for age and socio-economic and lifestyle factors. RESULTS: AIDA amongst women was associated with a nearly fourfold increased risk of MI [hazard ratio (HR) 3.63, 95% confidence interval (CI) 2.21-5.96) compared to nondiabetic participants, whereas no excess risk was found in men with AIDA (HR 1.30, 95% CI 0.70-2.52). By contrast, type 2 diabetes was associated with an increased MI risk in both men (HR 1.92, 95% CI 1.62-2.26) and women (HR 2.39, 95% CI 1.98-2.89). The metabolic profile was more favourable in patients with AIDA than in those with type 2 diabetes, but glycaemic control was worse. Multivariable models and sensitivity analyses suggest that these results were robust. CONCLUSIONS: Women with AIDA were more likely to develop MI, compared to men with AIDA and both men and women with type 2 diabetes. Further investigations are warranted to confirm this gender difference.

Anxiety, depression and timing of insulin treatment among people with type 2 diabetes: Nine-year follow-up of the Nord-Trøndelag Health Study, Norway.

BACKGROUND: Depression and anxiety have been found to be predictors of poor health outcomes in diabetes, but mechanisms are still unclear. AIMS: To examine whether symptoms of anxiety and depression were associated with timing of initiating insulin therapy. METHODS: A cohort study of insulin-naive particpants with type 2 dabetes completed the Hospital Anxiey and Depression Scale, HADS-A (n = 731) and/or the HADS-D (n = 768) in the communy-based Nord-Trøndelag Health Study (1995-1997). Information on insulin initiation was retrieved from the Norwegian Prescription Database from January 1, 2004 to November 21, 2012. Cox regression analyses were used to estimate the association between symptoms of anxiety, depression and time to insulin initiation. RESULTS: At baseline, 19% reported anxiety symptoms (score≥8) and 18% depressive symptoms (score≥8). After a mean follow-up of 4.4 (SD 3.6) years, 337 (40%) participants had started insulin therapy. After adjustment for sociodemographic and clinical variables, anxiety symptoms were associated with later initiation of insulin therapy (HR 0.70, 95% CI 0.49-0.99), while depressive symptoms were not. Considering groups simultaneously, having both elevated depressive and elevated anxiety symptoms was associated with later time to insulin initiation (HR 0.62, 95% CI 0.39-0.99), while having only anxiety symptoms (without depressive) HR 0.81, 95% CI 0.50-1.32) or only depressive symptoms (without anxiety) (HR 1.08, 95% CI 0.68-1.72) were not. CONCLUSIONS: Anxiety was associated with a later initiation of insulin, while depressive symptoms were not. Persons with both elevated levels of anxiety and depression were also less likely to start insulin therapy. These results need further testing in other prospective studies.

Trends in overweight and obesity over 22 years in a large adult population: the HUNT Study, Norway.

Some reports indicate that the obesity epidemic may be slowing down or halting. We followed body mass index (BMI) and waist circumference (WC) in a large adult population in Norway (n = 90 000) from 1984-1986 (HUNT1) through 1995-1997 (HUNT2) to 2006-2008 (HUNT3) to study whether this is occurring in Norway. Height and weight were measured with standardized and identical methods in all three surveys; WC was also measured in HUNT2 and HUNT3. In the three surveys, mean BMI increased from 25.3 to 26.5 and 27.5 kg m-2 in men and from 25.1 to 26.2 and 26.9 kg m-2 in women. Increase in prevalence of obesity (BMI ≥ 30 kg m-2) was greater in men (from 7.7 to 14.4 and 22.1%) compared with women (from 13.3 to 18.3 and 23.1%). In contrast, women had a greater increase in abdominal obesity (WC ≥ 102 cm for men and WC ≥ 88 cm for women). There was a continuous shift in the distribution curve of BMI and WC to the right, demonstrating that the increase in body weight was occurring in all weight groups, but the increase of obesity was greatest in the youngest age groups. Our data showed no signs of a halt in the increase of obesity in this representative Norwegian population.

Cohort Profile: the HUNT Study, Norway.

The HUNT Study includes large total population-based cohorts from the 1980ies, covering 125 000 Norwegian participants; HUNT1 (1984-86), HUNT2 (1995-97) and HUNT3 (2006-08). The study was primarily set up to address arterial hypertension, diabetes, screening of tuberculosis, and quality of life. However, the scope has expanded over time. In the latest survey a state of the art biobank was established, with availability of biomaterial for decades ahead. The three population based surveys now contribute to important knowledge regarding health related lifestyle, prevalence and incidence of somatic and mental illness and disease, health determinants, and associations between disease phenotypes and genotypes. Every citizen of Nord-Trøndelag County in Norway being 20 years or older, have been invited to all the surveys for adults. Participants may be linked in families and followed up longitudinally between the surveys and in several national health- and other registers covering the total population. The HUNT Study includes data from questionnaires, interviews, clinical measurements and biological samples (blood and urine). The questionnaires included questions on socioeconomic conditions, health related behaviours, symptoms, illnesses and diseases. Data from the HUNT Study are available for researchers who satisfy some basic requirements (www.ntnu.edu/hunt), whether affiliated in Norway or abroad.

Alcohol consumption is associated with reduced risk of Type 2 diabetes and autoimmune diabetes in adults: results from the Nord-Trøndelag health study.

AIMS: We investigated the influence of different aspects of alcohol consumption on the risk of Type 2 diabetes and autoimmune diabetes in adults. METHODS: We used data from the Nord-Trøndelag Health Survey (HUNT) study, in which all adults aged ≥ 20 years from Nord-Trondelag County were invited to participate in three surveys in 1984-1986, 1995-1997 and 2006-2008. Patients with diabetes were identified using self-reports, and participants with onset age ≥ 35 years were classified as having Type 2 diabetes if they were negative for anti-glutamic acid decarboxylase (n = 1841) and as having autoimmune diabetes if they were positive for anti-glutamic acid decarboxylase (n = 140). Hazard ratios of amount and frequency of alcohol use, alcoholic beverage choice, and binge drinking and alcohol use disorders were estimated. RESULTS: Moderate alcohol consumption (adjusted for confounders) was associated with a reduced risk of Type 2 diabetes in men, but not in women (hazard ratio for men 10-15 g/day 0.48, 95% CI 0.28-0.77; hazard ratio for women ≥ 10 g/day 0.81, 95% CI 0.33-1.96). The reduced risk was primarily linked to consumption of wine [hazard ratio 0.93, 95% CI 0.87-0.99 (per g/day)]. No increased risk was seen in participants reporting binge drinking or in problem drinkers. The results were also compatible with a reduced risk of autoimmune diabetes associated with alcohol consumption [hazard ratio 0.70, 95% CI 0.45-1.08 (frequent consumption) and hazard ratio 0.36, 95% CI 0.13-0.97 (2-7 g/day)]. CONCLUSIONS: Moderate alcohol consumption associates with reduced risk of both Type 2 diabetes and autoimmune diabetes. A protective effect of alcohol intake may be limited to men. High alcohol consumption does not seem to carry an increased risk of diabetes.

Time dynamics of autoantibodies are coupled to phenotypes and add to the heterogeneity of autoimmune diabetes in adults: the HUNT study, Norway.

AIMS: The aetiology of latent autoimmune diabetes in adults (LADA), assessed by autoimmune markers, is insufficiently clarified. We cross-sectionally investigated the prevalence and prospectively the prediabetic and postdiabetic presence of antibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 and zinc transporter 8 in LADA and in type 1 diabetes. METHODS: We included 208 'classic' type 1, 161 LADA and 302 type 2 diabetic cases from the second (HUNT2: 1995­1997) and third (HUNT3: 2006­2008) Nord-Trøndelag health surveys. Prospective data were available for 59 type 1, 44 LADA and 302 type 2 diabetic cases followed from HUNT2 to HUNT3. From HUNT3, 24 type 1 diabetic and 31 LADA incident cases were available. RESULTS: Cross-sectionally, 90% of LADA cases were positive for only one antibody (10% multiple-antibodypositive). Prospectively, 59% of GADA-positive LADA patients in HUNT2 were no longer positive in HUNT3. LADA patients who became negative possessed less frequently risk HLA haplotypes and were phenotypically more akin to those with type 2 diabetes than to those who stayed positive. Still, those losing positivity differed from those with type 2 diabetes by lower C-peptide levels (p = 0.009). Of incident LADA cases in HUNT3, 64% were already antibody-positive in HUNT2, i.e. before diabetes diagnosis. These incident LADA cases were phenotypically more akin to type 1 diabetes than were those who did not display positivity in HUNT2. CONCLUSION/INTERPRETATION: The pattern of antibodies, the postdiabetic loss or persistence as well as the prediabetic absence or presence of antibodies influence LADA phenotypes. Time-dependent presence or absence of antibodies adds new modalities to the heterogeneity of LADA.

No effect by the common gene variant rs10830963 of the melatonin receptor 1B on the association between sleep disturbances and type 2 diabetes: results from the Nord-Trøndelag Health Study.

AIMS/HYPOTHESIS: Genetic variation in the melatonin receptor 1B (MTNR1B) is associated with type 2 diabetes. Melatonin contributes to the regulation of sleep, and sleep problems are a documented risk factor for type 2 diabetes. The aim of this study was to investigate whether the MTNR1B gene variant rs10830963 is associated with sleep problems and whether this variant contributes to the association between sleep disturbances and type 2 diabetes. METHODS: This was a case-control study nested within the population-based Nord-Trøndelag Health Study, including 1,322 prevalent cases of type 2 diabetes and 1,447 controls. In addition, prospective data were available for 838 incident cases and 1,133 controls. Genotyping was done by TaqMan single-nucleotide polymorphism allelic discrimination analysis. ORs and 95% CIs were calculated using logistic regression models. RESULTS: Our findings confirm an association between sleep disturbances and type 2 diabetes (OR 1.69, 95% CI 1.22-2.33, p = 0.0016) and between the risk allele of rs10830963 and type 2 diabetes (OR 1.12, 95% CI 1.00-1.27, p = 0.0579). There was a tendency for an association between the risk allele and prevalence of sleep problems (specifically early awakening). However, the risk allele did not influence the association of sleep problems with diabetes, which was unaltered after adjustment for the MTNR1B risk allele (OR 1.69, 95% CI 1.23-2.34, p = 0.0014). Results based on prospective data were similar, although non-significant. CONCLUSIONS/INTERPRETATION: Our findings do not support participation of the MTNR1B gene variant rs10830963 in the well documented association between sleep disturbances and type 2 diabetes.

Urinary albumin excretion in latent autoimmune diabetes in adults (LADA) is more similar to type 2 than type 1 diabetes: results of the Nord-Trøndelag Health Study 1995-1997.

AIM: As it is unclear, whether or not, urinary albumin excretion (UAE) differs between patients classified as latent autoimmune diabetes in adults (LADA) and other forms of diabetes, our study aimed to investigate the distribution of the albumin-to-creatinine ratio (ACR) in LADA compared with those in the "classical" types 1 (T1D) and 2 (T2D) diabetes. METHODS: We used data from the Nord-Trøndelag Health Study (HUNT) (n=64,931) of 1995-1997. ACR (mg/mmol) was measured in three urine samples from all diabetic patients (n=1525) and from 5% of the non-diabetic study population (n=2104). We calculated the geometric means and 95% confidence intervals (CI) using a general linear model. RESULTS: The unadjusted mean ACR in LADA was similar to that in T2D (1.45, CI: 1.23-1.71 vs 1.41, CI: 1.33-1.49, respectively) but was significantly higher than those in T1D (0.99, CI: 0.83-1.19; P=0.002) and non-diabetics (0.72, CI: 0.69-0.74; P<0.001). These results remained similar even after multiple adjustments. CONCLUSION: In this cross-sectional study, the ACR in LADA and in T2D were similar and higher than in T1D. This similarity between LADA and T2D makes it unlikely that the autoimmune processes that operate in LADA promote albuminuria.

Metabolic syndrome and risk of mortality in middle-aged versus elderly individuals: the Nord-Trøndelag Health Study (HUNT).

AIMS/HYPOTHESIS: Recent reviews indicate that the metabolic syndrome is a risk factor for cardiovascular disease and mortality, but evidence is scarce in elderly individuals. We therefore examined the relationship between the metabolic syndrome and mortality rates among individuals aged 40-59, 60-74 and 75-89 years. We also examined whether the syndrome was associated with mortality rates over and above the Framingham risk score. METHODS: We studied prospectively 6,748 men and women who participated in the Nord-Trøndelag Health Study, Norway, from 1995 to 1997 (HUNT 2) and defined the metabolic syndrome by the International Diabetes Federation criteria. RESULTS: During 53,617 person-years of follow-up (mean per person, 7.9 years), 955 individuals died, of whom 585 died from cardiovascular disease. Among individuals who were 40-59 years of age at baseline, the presence of the metabolic syndrome was associated with increased relative risk of cardiovascular and total mortality (age- and sex-adjusted hazard ratios 3.97 [95% CI: 2.00-7.88] and 2.06 [1.35-3.13], respectively, equivalent to population-attributable risks of 20.7 and 14.2%, respectively). The Framingham risk score accounted for less than one-third of the effect of metabolic syndrome on mortality rates. After the age of 60 years, the metabolic syndrome was not associated with increased mortality rates. We found a significant interaction between the metabolic syndrome and age on the relative risk of mortality. Results were confirmed in a sub-sample without cardiovascular disease at baseline. CONCLUSIONS/INTERPRETATION: The metabolic syndrome is a risk factor for mortality, over and above the Framingham risk score, in middle-aged, but not in elderly individuals.

No association of depression and anxiety with the metabolic syndrome: the Norwegian HUNT study.

OBJECTIVE: To examine the associations of depression and anxiety with the metabolic syndrome. METHOD: Cross-sectional study of 9571 participants aged 20-89 years in the Nord-Trøndelag Health Study (HUNT 2). We assessed anxiety and depression with the Hospital Anxiety and Depression Scale and the metabolic syndrome with the International Diabetes Federation criteria. RESULTS: Despite generous statistical power and use of both continuous and categorical approaches, we found no association between anxiety or depression and the metabolic syndrome in models adjusted for age, gender, educational level, smoking, physical activity and pulse rate. When adjusted for age and gender only, we found a weak positive association for depression when a continuous measure was used, but not at the case level. The findings were similar across sexes, and robust for exclusion of cardiovascular disease and antidepressants. CONCLUSION: In this largest study to date we found no association of anxiety and depression with the metabolic syndrome.

Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population-based study--the HUNT study.

UNLABELLED: We studied the impact of genetic and traditional risk factors for type 2 diabetes in a large, population-based study from Nord-Trøndelag county in Norway (HUNT), in both cross-sectional and prospective design. MATERIAL AND METHODS: 65,905 individuals participated in the HUNT study. We studied a randomly selected group of 869 individuals with self-reported diabetes or non-fasting serum glucose >or=11.1 mmol/L and 2,080 non-diabetic control subjects with non-fasting serum glucose <5.5 mmol/L. Four candidate polymorphisms in the three genes TCF7L2 (rs12255372 and rs7903146), PPARG (rs1801282), KCNJ11 (rs5219) and traditional risk factors were studied. RESULTS: Risk alleles of the TCF7L2 gene showed increased risk of diabetes even when controlled for traditional diabetes risk factors (diabetes in family, waist circumference, physical activity, BMI, SBP and total and HDL-cholesterol) in both a cross-sectional and prospective setting (cross-sectional: rs12255372 OR 1.61 (1.31-1.99), rs7903146 OR 1.48 (1.20-1.83) and prospective: rs12255372 OR 1.59 (1.22-2.07), rs7903146 OR 1.47 (1.11-1.93)). The risk alleles of TCF7L2 indicated impaired beta-cell function in patients and control subjects. The population attributable risks for diabetes with TCF7L2 risk alleles were 15 % and with diabetes in a first-degree relative 31 %. CONCLUSION: The risk alleles of the TCF7L2 gene (rs12255372 and rs7903146) were strongly associated with type 2 diabetes, even after controlling for traditional risk factors in both a cross-sectional and prospective setting. These risk alleles were associated with indices of reduced beta-cell function.

Prevalence of HNF1A (MODY3) mutations in a Norwegian population (the HUNT2 Study).

AIMS: Previous reports have indicated that maturity-onset diabetes of the young (MODY) caused by hepatocyte nuclear factor 1A (HNF1A) mutations (MODY3) is the most common MODY subtype in Northern Europe, but population-based prevalence estimates are lacking. We sought to determine the prevalence of HNF1A-MODY in diabetic subjects of a defined Norwegian population (the HUNT2 Study). METHODS: Of the 1972 diabetic HUNT2 subjects, we identified a subgroup of 43 suspected MODY cases based on information on family history, disease onset and anti-glutamic acid decarboxylase autoantibody status. These cases were considered a discovery group for HNF1A mutations and underwent full DNA sequencing. Subsequently, the entire cohort of diabetic HUNT2 subjects was screened for three selected HNF1A mutations. Possible founder effects were examined using the Norwegian MODY Registry. RESULTS: Three subjects from the discovery group harboured HNF1A mutations. Two subjects had the previously described R229Q mutation, one had a novel S6N alteration, whereas the HNF1A hot-spot mutation P291fsinsC was not identified. Genotyping the cohort of diabetic HUNT2 subjects identified five additional R229Q-positive subjects. Microsatellite analysis performed for all R229Q-positive probands of the Norwegian MODY Registry and those found in the HUNT2 population revealed that 17 of 18 (94%) had genotypes consistent with a common haplotype. CONCLUSIONS: Clinical MODY criteria were fulfilled in 2.2% of diabetic HUNT2 subjects. The minimum prevalence of HNF1A-MODY among diabetic HUNT2 subjects was 0.4%. Because of founder effects, registry-based prevalence studies probably need to be very large and they should also include prospectively collected phenotypes and extensive mutation screening to establish the true prevalence of MODY.

Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study).

AIMS/HYPOTHESIS: Recent genome-wide association studies performed in selected patients and control participants have provided strong support for several new type 2 diabetes susceptibility loci. To get a better estimation of the true risk conferred by these novel loci, we tested a completely unselected population of type 2 diabetes patients from a Norwegian health survey (the HUNT study). METHODS: We genotyped single nucleotide polymorphisms (SNPs) in PKN2, IGFBP2, FLJ39370 (also known as C4ORF32), CDKAL1, SLC30A8, CDKN2B, HHEX and FTO using a Norwegian population-based sample of 1,638 patients with type 2 diabetes and 1,858 non-diabetic control participants (the HUNT Study), for all of whom data on BMI, WHR, cholesterol and triacylglycerol levels were available. We used diabetes, measures of obesity and lipid values as phenotypes in case-control and quantitative association study designs. RESULTS: We replicated the association with type 2 diabetes for rs10811661 in the vicinity of CDKN2B (OR 1.20, 95% CI: 1.06-1.37, p=0.004), rs9939609 in FTO (OR 1.14, 95% CI: 1.04-1.25, p=0.006) and rs13266634 in SLC30A8 (OR 1.20, 95% CI: 1.09-1.33, p=3.9 x 10(-4)). We found borderline significant association for the IGFBP2 SNP rs4402960 (OR 1.10, 95% CI: 0.99-1.22). Results for the HHEX SNP (rs1111875) and the CDKAL1 SNP (rs7756992) were non-significant, but the magnitude of effect was similar to previous estimates. We found no support for an association with the less consistently replicated FLJ39370 or PKN2 SNPs. In agreement with previous studies, FTO was most strongly associated with BMI (p=8.4 x 10(-4)). CONCLUSIONS/INTERPRETATION: Our data show that SNPs near IGFBP2, CDKAL1, SLC30A8, CDKN2B, HHEX and FTO are also associated with diabetes in non-selected patients with type 2 diabetes.

Headache prevalence related to diabetes mellitus. The Head-HUNT study.

In patients with diabetes mellitus (DM), there are changes in vascular reactivity and nerve conduction that may be relevant for migraine pathophysiology. However, previous studies on the relationship between headache and DM have shown conflicting results. The aim of the present study was to investigate a possible association between headache and DM in a large population-based cross-sectional study. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CIs). Prevalence OR of migraine was lower amongst persons with DM compared with those without DM, the OR being 0.4 (95% CI: 0.2-0.9) for type 1 and 0.7 (95% CI: 0.5-0.9) for type 2 DM. Furthermore, OR of headache were lower amongst those with duration of DM > or = 13 years compared with those who had got DM the last 3 years, OR 0.6 (95% CI: 0.4-0.9). The analyses revealed no clear associations between non-migrainous headache and DM. The reason for the inverse relationship between migraine and DM is unknown, but might be related to pathophysiological abnormalities in patients with DM that protect against migraine.

Age, overweight and physical inactivity increase the risk of latent autoimmune diabetes in adults: results from the Nord-Trøndelag health study.

AIMS/HYPOTHESIS: Latent autoimmune diabetes (LADA) is a common form of diabetes, yet the risk factors are poorly characterised. The aim of this study was to investigate the influence of age, overweight and physical activity on the risk of LADA. METHODS: We analysed age, overweight and physical inactivity and the incidence of LADA in 38,800 men and women, observed between 1984 and 1986 and 1995 and 1997 as part of the Nord-Trøndelag Health Survey. We also compared such factors with incident cases of type 2 (n = 738) and 'classic' type 1 diabetes (n = 18). Patients classified as LADA (n = 81) had antibodies against GAD and were insulin independent at diagnosis. RESULTS: The proportion of those who were older, overweight and inactive before diagnosis was almost identical in LADA and type 2 diabetes patients. BMI >or=30 kg/m(2) was strongly associated with LADA incidence (relative risk [RR] = 15.0, 95% CI 7.51-29.97). The association was similar for type 2 diabetes (RR = 15.37, 95% CI 12.07-19.57) but not for type 1 diabetes. Similarly, age (>or=60 years) was an important risk factor for LADA (RR = 5.62, 95% CI 2.36-13.4) as well as for type 2 diabetes (RR = 6.78, 95% CI 5.07-9.06) in contrast to type 1 diabetes. Physical inactivity was associated with an increased risk of both LADA and type 2 diabetes. CONCLUSIONS/INTERPRETATION: This study suggests that increased age, overweight and physical inactivity are as strong risk factors for LADA as for type 2 diabetes. These findings suggest a role for insulin resistance in the pathogenesis of LADA.

Change in height, weight and body mass index: Longitudinal data from the HUNT Study in Norway.

OBJECTIVE: The aim of this study was to analyse changes in body weight and height, and the changes in the prevalence of overweight and obesity. DESIGN: Prospective population based study with 11-year follow-up. SUBJECTS: Norwegian men (n=21565) and women (n=24337) aged 20 years or more who participated in two health surveys, the first in 1984-1986 and the other in 1995-1997. MEASUREMENTS: Height and weight were measured by using standardised procedures at both surveys, and we computed body mass index (BMI) as weight in kilo divided by the squared value of height in meters. RESULTS: Participants who were younger than 50 years at the first survey showed a large increase in body weight, and men and women aged 20-29 years increased their weight with an average of 7.9 kg and 7.3 kg, respectively. Contradictory, participants who were 70 years or older had on average a weight loss. The prevalence of overweight (BMI=25.0-29.9 kg/m(2)) and obesity (BMI>/=30 kg/m(2)) increased between the surveys, especially in the youngest age groups. Overall, the proportion classified as obese increased from 6.7 to 15.5% among men and from 11.0 to 21.0% among women. Some of this increase was due to a reduction in height, which was most pronounced in the oldest age groups. CONCLUSION: During approximately 10 years, body weight increased in all age groups below 70 years, and the prevalence of overweight and obese persons was approximately 20% higher at the second survey compared with the first survey.

Change in body mass index and its impact on blood pressure: a prospective population study.

BACKGROUND: Overweight and obesity increase the risk of elevated blood pressure, but the knowledge of the effect of weight change on blood pressure is sparse. OBJECTIVE: To investigate the association between change in body mass index (BMI) and change in diastolic blood pressure (DBP), systolic blood pressure (SBP), and hypertension status. DESIGN: Two population-based cross-sectional studies, one in 1984-86 and the other in 1995-97. SETTING: The Nord-Trondelag Health Study (HUNT). PARTICIPANTS: We included 15,971 women and 13,846 men who were 20 y or older at the first survey, without blood pressure medication at both surveys and without diabetes, cardiovascular disease or dysfunction in daily life at baseline. MEASUREMENTS: Weight, height and blood pressure were measured standardised. Change in BMI was categorised as stable (initial BMI+/-0.1 kg/m2 each follow-up year), increased or decreased, and BMI was categorised by using World Health Organisation's categorisation (underweight BMI: <18.5 kg/m2, normal weight BMI: 18.5-24.9 kg/m2, overweight BMI: 25.0-29.9 kg/m2, obesity BMI> or =30 kg/m2). RESULTS: An increase in BMI and a decrease in BMI were significantly associated with increased and decreased SBP and DBP, respectively, compared to a stable BMI in both genders and all age groups, although the strongest effect was found among those who were 50 y and older. The adjusted odds ratio for having hypertension at HUNT 2 was 1.8 (95% confidence interval (CI): 1.5, 2.2) among women and 1.6 (95% CI: 1.4,1.8) among men aged 20-49 y who increased their BMI compared to those who had stable BMI. A similar, but weaker association was found among women and men aged 50 y or more. The mean change in both SBP and DBP was higher for those who changed BMI category from first to the second survey than for those who were in the same BMI class at both surveys. CONCLUSIONS: Our result supports an independent effect of change in BMI on change in SBP and DBP in both women and men, and that people who increase their BMI are at increased risk for hypertension.

Weight change and mortality: the Nord-Trøndelag Health Study.

OBJECTIVES: The prevalence of obesity is increasing. Overweight and obese people have increased mortality compared with normal weight people. We investigated the effect of weight change on mortality. DESIGN: Prospective population study. SETTING: We utilized data from two large population-based health studies conducted in 1984-86 and 1995-97 respectively. Cox proportional hazards models were used to calculate mortality rate ratios (RRs) with 95% confidence intervals (CIs) between people with a stable weight and people who lost or gained weight. Subjects. Totally 20,542 men and 23,712 women aged 20 years or more, without cardiovascular disease or diabetes at the first survey and without a history of cancer at the second survey were followed up on all-cause mortality for 5 years after the second survey. RESULTS: We found no association between weight gain and mortality. People who lost weight had a higher total mortality rate compared with those who were weight stable [RR was 1.6 (95% CI: 1.4-1.8) in men and 1.7 (95% CI: 1.5-2.0) in women]. Similar associations were found for cardiovascular and noncardiovascular mortality. Additional analysis showed a linear increase in mortality rates across categories of weight loss for both men and women (P < 0.001). There was a statistically significant interaction between weight change and initial BMI, but only amongst men (P = 0.001). CONCLUSIONS: Weight loss, but not weight gain, was associated with increased mortality amongst men and women. Although underlying undiagnosed disease is the most plausible explanation for this finding, the similar associations found for total mortality, cardiovascular mortality, and noncardiovascular mortality makes the causal pathway somewhat enigmatic.

Smoking is associated with an increased risk of type 2 diabetes but a decreased risk of autoimmune diabetes in adults: an 11-year follow-up of incidence of diabetes in the Nord-Trøndelag study.

AIMS/HYPOTHESIS: We compared the association between smoking habits and later occurrence of type 2 diabetes on the one hand and between smoking and diabetes with autoimmunity on the other hand. METHODS: We used data from a prospective study of 11-year cumulative incidence of diabetes in the Nord-Trøndelag Health Survey. RESULTS: Confirming previous reports, heavy smoking (>/=20 cigarettes per day) carried an increased relative risk (RR) of type 2 diabetes (n=738, RR=1.64, 95% CI: 1.12-2.39). In contrast, smoking reduced the risk of latent autoimmune diabetes in adults (LADA) and of traditional type 1 diabetes (LADA n= 81, RR=0.25, 95% CI: 0.11-0.60; type 1 diabetes, n=18, RR=0.17, 95% CI: 0.04-0.73). CONCLUSIONS/INTERPRETATIONS: The results indicate that nicotine influences autoimmune processes in human diabetes.